The Department of Justice, the Department of Education, and the Department of Health and Human Services have sent a joint letter to the nation’s medical schools, dental schools, nursing schools, and other health-related schools regarding hepatitis B discrimination.

In the letter, the departments express concern that some health-related schools may be making enrollment decisions based on an incorrect understanding of the hepatitis B virus, resulting in discrimination.

The letter updates schools on the latest recommendations from the Centers for Disease Control and Prevention (CDC) regarding the participation of students with hepatitis B in health-related schools. The letter also emphasizes the importance of CDC’s recommendations, especially as they relate to the schools’ obligation to comply with federal laws prohibiting discrimination on the basis of disability, race, color, and national origin.

Approximately 800,000 to 1.4 million people in the United States have hepatitis B. Asians, Native Hawaiians, and Pacific Islanders make up roughly 4.5 percent of the U.S. population, but represent 50 percent of the persons with hepatitis B in the United States.

The letter cites to a March 2013 settlement agreement that the Justice Department reached with a medical school and a school of osteopathic medicine resolving allegations that the schools violated the Americans with Disabilities Act by excluding previously-accepted applicants with hepatitis B from their programs.

The updated CDC recommendations, based on the most current scientific information, dispel many myths associated with hepatitis B and provide guidance to health-related schools on managing students with the virus. The CDC also notes that since the last update of the recommendations in 1991, there have been no reports of hepatitis B transmission in the United States or other developed countries from medical or dental students to patients. Among other recommendations, the CDC recommends that chronic hepatitis B virus infection, in itself, should not preclude the study or practice of medicine, surgery, dentistry, or allied health professions.

“The Justice Department strongly urges health-related schools to review the CDC’s recommendations and to ensure that their policies and practices comply with federal nondiscrimination laws,” says Jocelyn Samuels, principal deputy assistant attorney general for the Civil Rights Division of the Justice Department. “Applicants and students with hepatitis B should not have to face exclusion on the basis of unfounded fears and stereotypes, and the Justice Department will not tolerate it.”

“Both public health and civil rights will be promoted when medical schools rely on the most recent scientific information, not overbroad generalizations, in dealing with medical students with hepatitis B,” says Seth Galanter, acting assistant secretary for civil rights in the Department of Education.

Leon Rodriguez, director of the Office for Civil Rights in the Department of Health and Human Services, agrees that health-related schools must ensure that they do not deny equal access to individuals based on discrimination, adding, “The CDC recommendations promote public health and safety while also offering guidance on the management of students with hepatitis B. Our agencies place considerable weight on this guidance in our enforcement of Federal civil rights laws.”

The Departments of Justice, Education, and Health and Human Services share responsibility for protecting the rights of students and applicants with disabilities, including those with hepatitis B, in schools of higher education by enforcing titles II and III of the Americans with Disabilities Act and Section 504 of the Rehabilitation Act. These laws prohibit covered postsecondary institutions from discriminating on the basis of disability and from refusing to make reasonable modifications to their policies, practices, or procedures when necessary to avoid discrimination on the basis of disability, unless such modifications would fundamentally alter the nature of the program or the services provided. The Departments of Justice, Education, and Health and Human Services also enforce Title VI of the Civil Rights Act, which prohibits discrimination on the basis of race, color, or national origin in programs and activities receiving federal financial assistance, including those of health-related schools.

WINSTON-SALEM, N.C. – June 19, 2013 – The role of dietary fructose in the development of obesity and fatty liver diseases remains controversial, with previous studies indicating that the problems resulted from fructose and a diet too high in calories.

However, a new study conducted in an animal model at Wake Forest Baptist Medical Center showed that fructose rapidly caused liver damage even without weight gain. The researchers found that over the six-week study period liver damage more than doubled in the animals fed a high-fructose diet as compared to those in the control group.

The study is published in the June 19 online edition of the American Journal of Clinical Nutrition.

"Is a calorie a calorie? Are they all created equal? Based on this study, we would say not," said Kylie Kavanagh, D.V.M., assistant professor of pathology-comparative medicine at Wake Forest Baptist and lead author of the study.

In a previous trial which is referenced in the current journal article, Kavanagh's team studied monkeys who were allowed to eat as much as they wanted of low-fat food with added fructose for seven years, as compared to a control group fed a low-fructose, low-fat diet for the same time period. Not surprisingly, the animals allowed to eat as much as they wanted of the high-fructose diet gained 50 percent more weight than the control group. They developed diabetes at three times the rate of the control group and also developed hepatic steatosis, or non-alcoholic fatty liver disease.

The big question for the researchers was what caused the liver damage. Was it because the animals got fat from eating too much, or was it something else?

To answer that question, this study was designed to prevent weight gain. Ten middle-aged, normal weight monkeys who had never eaten fructose were divided into two groups based on comparable body shapes and waist circumference. Over six weeks, one group was fed a calorie-controlled diet consisting of 24 percent fructose, while the control group was fed a calorie-controlled diet with only a negligible amount of fructose, approximately 0.5 percent.

Both diets had the same amount of fat, carbohydrate and protein, but the sources were different, Kavanagh said. The high-fructose group's diet was made from flour, butter, pork fat, eggs and fructose (the main ingredient in corn syrup), similar to what many people eat, while the control group's diet was made from healthy complex carbohydrates and soy protein.

Every week the research team weighed both groups and measured their waist circumference, then adjusted the amount of food provided to prevent weight gain. At the end of the study, the researchers measured biomarkers of liver damage through blood samples and examined what type of bacteria was in the intestine through fecal samples and intestinal biopsies.

"What surprised us the most was how quickly the liver was affected and how extensive the damage was, especially without weight gain as a factor," Kavanagh said. "Six weeks in monkeys is roughly equivalent to three months in humans."

In the high-fructose group, the researchers found that the type of intestinal bacteria hadn't changed, but that they were migrating to the liver more rapidly and causing damage there. It appears that something about the high fructose levels was causing the intestines to be less protective than normal, and consequently allowing the bacteria to leak out at a 30 percent higher rate, Kavanagh said.

One of the limitations of the study was that it only tested for fructose and not dextrose. Fructose and dextrose are simple sugars found naturally in plants.

"We studied fructose because it is the most commonly added sugar in the American diet, but based on our study findings, we can't say conclusively that fructose caused the liver damage," Kavanagh said. "What we can say is that high added sugars caused bacteria to exit the intestines, go into the blood stream and damage the liver.

"The liver damage began even in the absence of weight gain. This could have clinical implications because most doctors and scientists have thought that it was the fat in and around tissues in the body that caused the health problems."

The Wake Forest Baptist team plans to begin a new study using the same controls but testing for both fructose and dextrose over a longer time frame.

Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner

Action Points

Online registration rates in the U.S. increased dramatically after the Facebook organ donor initiative.

Note that the study raises the possibility that social media might be effectively utilized in other refractory public health problems in which communication and education are essential.

Despite years of media and public service campaigns appealing for organ donations, donor rates remained static while demand increased -- until Facebook, researchers reported.

On May 1, 2012, the social media website launched its organ donor initiative that allowed users to change their status to indicate "organ donor," triggering a link to their official state donor registry. On that day, there were 13,054 new online registrations, representing a 21.1-fold increase over the baseline average of 616 registrations daily, according to Andrew Cameron, MD, PhD, of the Johns Hopkins University School of Medicine, and colleagues.

The first-day effect ranged from 6.9-fold in Michigan to 108.9-fold in Georgia, with registration rates remaining elevated over the subsequent 12 days, they wrote online in the American Journal of Transplantation.

During the same time period, organ donor registrations through motor vehicle divisions (DMV) saw no increases, Cameron and colleagues noted.

However, Cameron cautioned in a statement that "the bump we saw did diminish over weeks, implying that more work is needed to assure sustainability or 'virality' in this case."

Nonetheless, "novel applications of social media may prove effective in increasing organ donation rates and likewise might be utilized in other refractory public health problems in which communication and education are essential," they wrote.

Registrations totaled 39,818 over the 13-day study period, 32,958 more than would have been expected from the baseline registration rate, researchers stated.

Before the advent of social media, organ donation awareness and registration was done through school-based campaigns, work site events, and at the DMV, the authors pointed out, leading to about 100 million people in the U.S. signing up as donors.

"While this number represents a signiﬁcant accomplishment, it still amounts to only around one-third of the country's population and has proved inadequate to meet the need of the growing number added to transplant waitlists," they explained.

Facebook collaborated with members of the transplant team at Johns Hopkins, the Living Legacy Foundation of Baltimore, and Donate Life America, to allow speciﬁcation of organ donor designation on their "Timeline" platform.

Cameron and colleagues then studied the number of Facebook organ donor profile updates for the month of May 2012. Data were available for online registration for 43 of 50 states and the District of Columbia. Alaska, Delaware, North Dakota, New Jersey, Pennsylvania, South Dakota, and West Virginia were excluded.

DMV data were available for Michigan, Montana, Texas and Washington for three days in early May 2012.

States with higher online registration rates before the Facebook organ donor initiative had higher rates of online registration after the initiative was introduced, the researchers stated. However, they had a lower proportional increase (a lower Facebook effect) than states with lower rates of online registration before the Facebook organ donor initiative was begun, they wrote.

The association between baseline registration and registration after the initiative was suggestive, but not statistically significant, with one additional registration per day per million people during baseline period associated with four additional registrations per million people on May 1 (95% CI minus 0.3-8.3, P=0.10).

Conversely, one additional registration per day per million people during baseline period was associated with a decrease in Facebook effect of 5.8 (95% CI, minus 8.7 -minus 3.0, P<0.001).

Study limitations included unknown durability of the Facebook effect, the authors wrote, and years will be required to register an increase in deceased organ donations from the social media effort. Also, the observational approach does not specify the extent donor registration was increased because of social versus conventional media.

"The next challenge for efforts like the organ donor initiative will be utilization of social media applications like Facebook, Twitter, YouTube, or Instagram more effectively and more durably," they concluded.

The U.S. Department of Health and Human Services (HHS) has released a new guideline to improve patient safety by reducing unexpected disease transmission through organ transplantation. This guideline updates the 1994 U.S. Public Health Service (PHS) guideline for preventing transmission of human immunodeficiency virus (HIV) through organ transplantation and adds guidance for reducing unexpected transmission of hepatitis B virus (HBV) and hepatitis C virus (HCV) through organ transplants.

The 2013 PHS Guideline for Reducing Human Immunodeficiency Virus, Hepatitis B Virus and Hepatitis C Virus Transmission through Organ Transplantation, published in Public Health Reports, recommends the use of more sensitive tests so that patients can be informed of risks to the greatest extent possible and protected from unintentional infections caused by transplanted organs.

The major changes from the previous PHS guideline are:

• Recommendation that donors be screened for both HBV and HCV, in addition to HIV. Although organ donors are routinely screened for HBV and HCV, there were no specific PHS recommendations for this screening included in the 1994 guideline.

• Recommendation for new, more sensitive laboratory testing. Since the 1994 PHS guideline was published, more sensitive tests for HIV, HBV and HCV have become available. The 2013 guideline recommends the use of more sensitive tests for living and deceased organ donors.

• Inclusion of a revised set of risk factors for HIV, HBV or HCV infection. Updated information about risk factors for these diseases can give clinicians a clearer picture about possible risks associated with donated organs to improve recipient informed consent, and in certain circumstances, to trigger more sensitive laboratory testing of the donor and recipients.

• Focus on organs and vessel conduits recovered for transplantation, and not on tissues, eyes or cellular products. The Food and Drug Administration (FDA) has implemented more comprehensive regulations for tissue and semen donors since the 1994 PHS guideline was published.

• Recommendation for a robust informed consent discussion between the transplant candidate (or medical decision maker) and the clinician. With the availability of more sensitive tests, doctors and patients can have a more thorough discussion about potential risks and benefits associated with accepting and rejecting individual organs.

Patients with chronic hepatitis C genotype 1 had higher sustained virologic response rates with better treatment duration adherence, while adherence to the assigned dosing interval had less impact in a recent study.

Researchers evaluated treatment adherence among 1,500 adult patients with chronic HCV genotype 1 treated with pegylated interferon-alfa and ribavirin. Adherence to the assigned duration of therapy and the thrice-daily dosing interval for boceprevir (BOC) were determined via patients’ dosing diaries and the amount of study drug dispensed to and returned from participants. The data was collected from the SPRINT-2 (n=1,097, treatment-naive participants) and RESPOND-2 (n=403, participants who failed prior peginterferon/ribavirin therapy) trials.

Sixty-three percent to 71% of patients were 80% adherent or better to treatment duration, and displayed sustained virologic response (SVR) rates between 86% and 90%. Among patients who were less than 80% adherent to duration, SVR rates were lower (8% to 32%; P<.0001). This difference was pronounced among those who had failed previous therapy (8% to 15%).

Between 42% to 52% of patients were 80% adherent or better to the thrice-daily BOC treatment interval. No significant difference in SVR rates was seen among treatment-naive patients (P=.195) according to interval adherence, but SVR rates were lower among nonadherent patients who had failed prior therapy (48% to 50% among those less than 60% adherent vs. 60% to 77%; P=.005).

Investigators said patients with 80% or better duration adherence had similar SVR rates to patients with high adherence to duration and interval (78% to 100% vs. 89% to 91%). Patients who were less adherent to duration had low SVR rates regardless of dosage adherence (0% to 50%).

“The present study shows that the ability to respond successfully to treatment was more dependent on adherence to the actual assigned duration of therapy,” researcher S.C. Gordon, MD, Henry Ford Hospital in Detroit, Mich., told Healio.com. “This ‘duration of viral negativity’ while on therapy translates to higher SVR rates. The study validates previous research, both in HIV therapy and in previous pegylated interferon and ribavirin therapies for hepatitis C, showing that patient adherence is key to a successful treatment course.”

The relatively obscure liver inflammation caused by hepatitis C virus (HCV) is a significant threat worldwide, and its prevalence is growing. It demands greater attention from both public health officials and drug developers.

The World Health Organization estimates that 170 million people are chronically infected with HCV, which is transmitted via blood-to-blood contact. In the developed world, the majority of people with HCV were infected prior to the 1992 introduction of sensitive screening tests which curtailed transmission from blood transfusions or organ transplants.

The course of infection is variable, but viral infection is chronic in the majority of cases and can result decades later in cirrhosis, liver failure and liver cancer. (In the developing world, where screening tests are less available, there is surely a higher but hard to estimate rate of new infections.)

In the United States, the estimates of about 3 million people chronically infected with HCV (based on the National Health and Nutrition Examination Survey) are probably an underestimate because the surveys do not include incarcerated or homeless people; the addition of these high-risk populations could increase prevalence estimates by 500,000–1,000,000. Moreover, because the disease is asymptomatic for a long period of time, only about 30% of HCV-infected people in the United States have been diagnosed.

The burden of HCV continues to grow because the peak of infections occurred in the 1970’s and 80’s before there was reliable testing of blood and organs for transplantation, and the complications of disease typically take 20-40 years to develop. Thus, HCV-related illness and deaths have been increasing and are projected to continue to grow significantly in coming years. The prevalence of HCV-related cirrhosis in the United States is expected to peak at 1 million individuals from the mid-2020s through the mid-2030s.

Many studies have shown that HCV infection results in significantly higher rates of death from liver-related diseases, as well as increased mortality from other causes, including cardiovascular and renal disease, which may be due to persistent inflammation and immune-complex deposition. Overall, HCV infection reduces life expectancy by 8-12 years. A 2011 Veterans Administration study found that achieving a “sustained virologic response” — no virus detectable in the blood six months after finishing treatment — after treatment of HCV was associated with a substantial reduction in the rates of decompensated cirrhosis, liver-related deaths and all-cause mortality. This is a clear demonstration that successful treatment of HCV infection improves patient outcomes.

However, the currently available treatment regimens for HCV leave much to be desired, and many asymptomatic patients forego treatment because of the poor safety profiles, tolerability, and low success rates of available drugs. Future all-oral regimens will eliminate many of these barriers to initiating treatment.

In recent years, the development of drugs to treat HCV infection has progressed rapidly. In May 2011, in combination with the then standard-of-care (pegylated-interferon-α and ribavirin), two novel direct-acting antiviral agents — MerckMerck’s Victrelis (boceprevir) and Vertex’s Incivek (telaprevir, marketed by Johnson and Johnson outside the United States as Incivo) — were approved to treat the most common subtype of HCV in the Western world.

Adoption of these agents was swift because they improved significantly the rate at which treated patients were cured of HCV and in many cases shortened the duration of treatment from 48 to 24 weeks. However, HCV treatment remained poorly tolerated, with frequent adverse events including flu-like symptoms (virtually universal with interferons), anemia, rash, and depression. Although sales exceeded $1 billion in the first year of commercialization, the use of the drugs has since declined as the backlog of patients needing treatment most urgently has been addressed.

We should soon have more effective and better-tolerated all-oral regimens that do not include interferon. Indeed, recent clinical data have shown very promising results with several interferon-free regimens, including different classes of drugs targeting various viral proteins and enzymes. These include drugs from Gilead and Abbott, both of which have Phase III trials under way for treatments which may be commercially available by 2015.

Data presented at recent medical meetings, including the American Association for the Study of Liver Diseases in November 2012, suggest that Gilead may be able develop an ideal HCV treatment regimen − a single, once-daily tablet that is well-tolerated, safe, and highly efficacious. At the least, Gilead is expected to capture a significant portion of the HCV market with regimens containing sofosbuvir (GS-7977), the nucleoside polymerase inhibitor acquired in the $11 billion takeover of Pharmasset. Bristol-Myers SquibbBMY +0.88%, Johnson and Johnson, Vertex and other companies are also working on all-oral HCV treatment regimens.

In addition to the clinical benefits, pharmaco-economic analyses also support treatment of HCV. Infected patients incur higher healthcare costs compared with a non-infected population matched by sex, age, and healthcare enrollment. Because costs are driven largely by end-stage liver disease, liver transplants and cancer, total HCV-related healthcare expenditures are likely to increase significantly over time as patients progress to more severe disease. The stringent assessment by the UK’s National Institute for Health and Clinical Excellence showed robust cost-effectiveness for treating HCV with either telaprevir or boceprevir. This analysis supported treatment of various patient sub-populations, including treatment-naïve patients with mild disease. Depending on the price points, the higher cure rates and reduced incidence of adverse events associated with oral direct-acting antivirals may lead to even greater cost-effectiveness in future.

Even new, cost-effective HCV treatments will have high overall costs, and the price of the various all-oral regimens for HCV may play a role in determining market share. Payers also are likely to have a significant influence on market dynamics. In the United States, in addition to requiring prior authorizations, payers are likely to manage costs aggressively by selecting a preferred regimen(s) and negotiating favorable pricing.

Given the history of the exposure to hepatitis C virus worldwide and the natural course of the infection and its complications, the disease is a public health and health care expense time bomb. That makes the availability of safer and more effective treatment options imperative. And while the costs of treating HCV will be high, in human and financial terms the costs of not treating the disease would be even higher.

Mina Marmor, Ph.D., CFA, is a financial analyst at Sectoral Asset Management inMontreal, an investment management firm that focuses exclusively on the health care sector. Henry Miller, a physician and molecular biologist, is the Robert Wesson Fellow in Scientific Philosophy and Public Policy at Stanford University’s Hoover Institution. He was the founding director of the FDA’s Office of Biotechnology and is a member of the Scientific Advisory Board of Sectoral. The statements and opinions expressed in the article are those of the authors as of the date of the article, are subject to change, and do not necessarily represent the views of Sectoral. The article does not constitute investment advice and is not a recommendation to buy, sell or hold the securities of any company mentioned in the article.

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